@article{8d533d828de04715ba01ebed2757dfbb,
title = "HOXB1 founder mutation in humans recapitulates the phenotype of Hoxb1 -/- mice",
abstract = "Members of the highly conserved homeobox (HOX) gene family encode transcription factors that confer cellular and tissue identities along the antero-posterior axis of mice and humans. We have identified a founder homozygous missense mutation in HOXB1 in two families from a conservative German American population. The resulting phenotype includes bilateral facial palsy, hearing loss, and strabismus and correlates extensively with the previously reported Hoxb1-/- mouse phenotype. The missense variant is predicted to result in the substitution of a cysteine for an arginine at amino acid residue 207 (Arg207Cys), which corresponds to the highly conserved Arg5 of the homeodomain. Arg5 interacts with thymine in the minor groove of DNA through hydrogen bonding and electrostatic attraction. Molecular modeling and an in vitro DNA-protein binding assay predict that the mutation would disrupt these interactions, destabilize the HOXB1:PBX1:DNA complex, and alter HOXB1 transcriptional activity.",
author = "Webb, {Bryn D.} and Sherin Shaaban and Harald Gaspar and Cunha, {Luis F.} and Schubert, {Christian R.} and Ke Hao and Robson, {Caroline D.} and Chan, {Wai Man} and Caroline Andrews and Sarah MacKinnon and Oystreck, {Darren T.} and Hunter, {David G.} and Iacovelli, {Anthony J.} and Xiaoqian Ye and Anne Camminady and Engle, {Elizabeth C.} and Jabs, {Ethylin Wang}",
note = "Funding Information: We are grateful to all individuals who generously participated in this study. We especially thank the Moebius Syndrome Foundation and the Children's Hospital Ophthalmology Foundation for their support. We are grateful to the Broad Institute for generating high-quality sequence data supported by funds from the National Human Genome Research Institute (grant #U54 HG003067, Eric Lander, PI). We would also like to thank Robert Cullen for his help with clinical assessment of family A. We appreciate Mihaly Mezei of Mount Sinai School of Medicine for his advice and guidance with protein modeling. Vincenzo Zappavigna of University of Modena and Reggio Emilia, Italy and Mark Featherstone of Nanyang Technological University, Singapore generously provided us with pAdML-ARE, pAdML, pSG-HOXB1, and pSG-PBX1A vectors. Kari Hemminki of the German Cancer Research Center, Heidelberg, Germany supplied us with German control DNAs. This research was supported in part by the Swiss National Science Foundation and National Institutes of Health (grants R01 EY15298, R01 HD018655, R01 HD018655, and U54 HG003067). E.C.E. is a Howard Hughes Medical Institute Investigator. ",
year = "2012",
month = jul,
day = "13",
doi = "10.1016/j.ajhg.2012.05.018",
language = "English",
volume = "91",
pages = "171--179",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "1",
}